Evidence map›Paper›PMID 39404052›Full record

ArticleNucleic acids research2024

Probing the mechanism of nick searching by LIG1 at the single-molecule level.

Surajit Chatterjee, Loïc Chaubet, Aafke van den Berg, Ann Mukhortava, Danah Almohdar, Jacob Ratcliffe, Mitchell Gulkis, Melike Çağlayan

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Surajit ChatterjeeDepartment of Biochemistry and Molecular Biology, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Loïc ChaubetLUMICKS B.V., 1059 CH, Paalbergweg 31105 AG, Amsterdam, The Netherlands.
Aafke van den BergLUMICKS B.V., 1059 CH, Paalbergweg 31105 AG, Amsterdam, The Netherlands.
Ann MukhortavaLUMICKS B.V., 1059 CH, Paalbergweg 31105 AG, Amsterdam, The Netherlands.
Danah AlmohdarDepartment of Biochemistry and Molecular Biology, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Jacob RatcliffeDepartment of Biochemistry and Molecular Biology, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Mitchell GulkisDepartment of Biochemistry and Molecular Biology, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.
Melike ÇağlayanDepartment of Biochemistry and Molecular Biology, University of Florida, 1200 Newell Drive, Gainesville, FL 32610, USA.ORCID 0000-0003-1107-1042

Funding

DNA ligase activities during base excision repair coordinationR35GM147111 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MELIKE CAGLAYAN · 2022 to 2026
$2.1M
NIGMS NIH HHS 1R35GM147111-01NIGMS NIH HHS R35 GM147111
6 · The paper itself

Abstract

DNA ligase 1 (LIG1) joins Okazaki fragments during the nuclear replication and completes DNA repair pathways by joining 3'-OH and 5'-PO4 ends of nick at the final step. Yet, the mechanism of how LIG1 searches for a nick at single-molecule level is unknown. Here, we combine single-molecule fluorescence microscopy approaches, C-Trap and total internal reflection fluorescence (TIRF), to investigate the dynamics of LIG1-nick DNA binding. Our C-Trap data reveal that DNA binding by LIG1 full-length is enriched near the nick sites and the protein exhibits diffusive behavior to form a long-lived ligase/nick complex after binding to a non-nick region. However, LIG1 C-terminal mutant, containing the catalytic core and DNA-binding domain, predominantly binds throughout DNA non-specifically to the regions lacking nick site for shorter time. These results are further supported by TIRF data for LIG1 binding to DNA with a single nick site and demonstrate that a fraction of LIG1 full-length binds significantly longer period compared to the C-terminal mutant. Overall comparison of DNA binding modes provides a mechanistic model where the N-terminal domain promotes 1D diffusion and the enrichment of LIG1 binding at nick sites with longer binding lifetime, thereby facilitating an efficient nick search process.

Indexed as

DNADNA Ligase ATPProtein BindingSingle Molecule ImagingDNA Breaks, Single-StrandedHumansMicroscopy, FluorescenceDNADNA Ligase ATPLIG1 protein, human

Identifiers

PMID39404052
PMCPMC11551761

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.